Paediatrica Indonesiana
p-ISSN 0030-9311; e-ISSN 2338-476X; Vol.57 No.1 (2017) p. 17-22; doi: 10.14238/pi57.1.2017.17-22.
Domperidone and maternal milk volume in mothers
of premature newborns
Tengku Ellya Fazilla, Guslihan Dasa Tjipta, Muhammad Ali, Pertin Sianturi
Abstract
Background Mothers of premature newborns often have diffi-
culty giving adequate breast milk volume to their infants. Dom-
peridone is an antagonist of peripheral dopamine receptors and
believed to increase breast milk production. In Indonesia, no study
has been done to date on the effect of domperidone on maternal
milk production in mothers of premature newborns.
Objective To evaluate the effect of domperidone on milk
production in mothers of premature newborns who failed to
lactate.
Methods A randomized controlled trial was conducted from July
to December 2012 in the Perinatology Unit, Haji Adam Malik
Hospital, Medan. Mothers of premature newborns were given
lactation counseling for 7 days in order to increase their milk
production. Mothers who failed to lactate after that time were
enrolled in the study. Fifty subjects were assigned to receive either
domperidone or a placebo for 7 days. Milk volume was measured
every 2 hours (from 7 am to 9 pm), in the 24 hours before starting
therapy, and on the 7th and 10th days (the 10th day being 3 days
after stopping therapy).
Results This study involved 25 mothers in the domperidone
groups and 25 others in placebo group. After 7 days of therapy,
mean breast milk volume was significantly higher in the dom-
peridone group than in the placebo group [181.6 (SD 80.2)
vs. 72.4 (SD 57.8) mL, respectively; 95%CI of differences
69.36 to 148.93; P=0.0001]. At day 10, breast milk produc-
tion remained significantly higher in the domperidone group.
Furthermore, in the domperidone group, no significant differ-
ence in mean breast milk volumes was noted between the 7th
and 10th days (P=0.65).
Conclusion In mothers of premature newborns who failed to
lactate, domperidone therapy for 7 days causes significantly
higher milk production compared to placebo. [Paediatr Indones.
2017:57:17-22. doi: 10.14238/pi57.1.2017.17-22].
Keywords: domperidone; premature newborn;
breast milk
Original Article
L
ow birth weight (LBW) and prematurity
are the leading causes of perinatal death in
Indonesian hospitals. In 2005, the percentage
of live birth infants with low birth weight
was 27.9% in Indonesia.1 Breast milk is the best
food for babies and preterm infants. Breastfeeding is
beneficial for babies, mothers, families, communities,
the environment, and countries. Breastfeeding is
expected to decrease the mortality and morbidity of
newborn preterm infants.2 Generally, mothers who
give birth to term infants produce sufficient milk in the
first week after delivery. However, mothers of preterm
babies often have inadequate milk production.
Various strategies to increase milk production have
been reported, such as relaxation techniques, use of
mechanical devices, and medications.3
Domperidone is a peripheral dopamine receptor
antagonist that is thought to work by blocking the
This study was presented at the Pertemuan Ilmiah Tahunan Ilmu Kesehatan
Anak VI/PIT IKA VI (The 6th Child Health Annual Scientific Meeting),
Solo, Central Java, Indonesia, October 8–10, 2013.
From the Department of Child Health, University of Sumatera Utara
Medical School/Haji Adam Malik Hospital, Medan, North Sumatera,
Indonesia.
Reprint requests to: dr. Tengku Ellya Fazilla, Department of Child Health,
University of Sumatera Utara Medical School/H. Adam Malik Hospital, Jl.
Bunga Lau No. 17, Medan, 20136. Tel. +6261-8361721 – 8365663; Fax.
+6261-8361721, E-mail: yonk_85@yahoo.com.
Paediatr Indones, Vol. 57, No. 1, January 2017• 17
 Tengku Ellya Fazilla et al: Domperidone and maternal milk volume in mothers of premature newborns
inhibitory effects of dopamine-mediated prolactin
secretion, thereby increasing milk production.4,5
There was still a few study on domperidone effects
to human milk production. In addition, there has
been no study on the effects of domperidone on milk
production in Indonesian mothers who gave birth to
preterm babies.
We aimed to evaluate milk production in
mothers who delivered preterm infants after admin-
istering domperidone. We also assessed for possible
relationships between milk production and maternal
age, gestational age, parity, method of delivery, and
educational level.
Methods
A randomized double-blind controlled trial was
conducted to assess the effect of domperidone (group
A) compared to that of placebo (group B) on milk
production in mothers who gave birth to preterm
babies. Subjects were recruited from the Perinatology
Unit, Haji Adam Malik Hospital, Medan from July to
December 2012.
The inclusion criteria were mothers aged 20 to
30 years who gave birth to infants with gestational
age < 37 weeks, as well as failure to lactate with
little or no improvement in milk production after
one week of lactation counseling, along with the
baby receiving feeding through a nasogastric tube.
Exclusion criteria were mothers who used medications
that affect domperidone (e.g., antacids, cimetidin,
ranitidine, famotidine, or nizatidine) or medications
that interact with domperidone (e.g., haloperidol
or lithium), mothers with mastitis, had undergone
breast surgery, had heart problems, obesity, diabetes,
or twins. Subjects were randomized into domperidone
and placebo groups by randomization tables.
Prior to enrollment, mothers underwent ECG
examinations to assess heart rhythm, followed by
lactation counseling for 7 days in order to maximize
breast milk production. If the counseling method
failed, then the mothers were eligible to participate in
the study. Domperidone was administered orally at a
dose of 10 mg, 3 times per day for 7 days. Tablets were
crushed, mixed with lactose, then put into capsules.
Placebo was lactose powder alone in capsules. All
subjects received 21 capsules to be taken 3 times daily
18 • Paediatr Indones, Vol. 57, No. 1, January 2017
for 7 days. A female health worker was employed to
supervise the administration of medication and help
subjects pump breast milk. Breast milk was collected
using a double breast pump (Medela ®), for 15 minutes
per pump cycle, done daily from 7:00 am to 9:00 pm,
every 2 hours. The collected breast milk was measured
by researchers and given to the preterm babies. The
volume of breast milk counted each day for 1 week.
Subjects noted their complaints during treatment,
such as dry mouth, headache, insomnia, abdominal
pain, diarrhea, nausea, or urinary retention. Breast milk
volume was measured at 24 hours prior to the start of
medication, 7 days after medication, and day 10 (3 days
after stopping the medication). Failure to lactate was
defined as decreased breast milk supply (more than
30% of maximum breast milk volume) and/or inability
to produce an adequate amount of breast milk to meet
the infant’s daily nutritional needs.4
We used unpaired T-test to compare mean
volumes of breast milk in the domperidone and
placebo groups. The comparison of mean breast milk
volumes on days 7 and 10 in both groups were analyzed
by paired T-test. Multivariate analysis was used to
determine the relationship between breast milk
volume and maternal age, gestational age, number of
children, method of delivery, and educational level.
Data processing was done with SPSS 15 software, and
results were considered to be significant for P values
<0.05 and 95% confidence intervals (CI). This study
based on intention to treat analysis.
Subjects provided informed consent for partici-
pation. This study was approved by the Ethics Com-
mittee of the University of Sumatera Utara Medical
School.
Results
At our hospital there were 107 preterm births from
July to December 2012, of whom 64 mothers had
inadequate breast milk volume. Twelve mothers were
excluded because their infants were of gestational age
> 37 weeks (4 mothers), they were aged > 30 years
(3 mothers), they were obese with BMI > 30 kg/m2
(3 mothers), or they delivered twins (2 mothers). Fifty-
two mothers who met the inclusion criteria underwent
ECG examination to screen for cardiac arrhythmias;
all had normal ECG results. These mothers underwent
 Tengku Ellya Fazilla et al: Domperidone and maternal milk volume in mothers of premature newborns

a lactation counseling program for 7 days to learn to
increase their breast milk production. Two infants
died during treatment due to respiratory distress from
hyaline membrane disease and sepsis. The remaining
50 mothers completed the lactation counseling
program, but failed to lactate. These mothers were
randomized into the domperidone or placebo groups,
each consisting of 25 mothers. During the study,
four mothers dropped out because their infants
died, three from the placebo group and one from the
domperidone group (Figure 1). The infants who died
were diagnosed with respiratory distress due to hyaline
membrane disease and sepsis.
Table 1 shows the characteristics of subjects.
Mean maternal ages in the domperidone and placebo
groups were 26 and 25 years, respectively. Mean
number of children borne by mother in both groups
was one, and mean gestational age in both groups
was 31 weeks. More subjects in the domperidone
group delivered vaginallly than by caesarean section,
but in the placebo group, more subjects underwent
caesarean section than vaginal delivery. Most
mothers in both groups finished high school (48%
and 52%, respectively) and 96% in both groups
were housewives. Mean infant birth weights in the
domperidone and placebo groups were 1,656 and
1,636 grams, respectively, while mean infant age at
hospital admission for both groups was 5 days. Mean
breast milk volume prior to therapy was 83.3 (SD
42.99) mL in the domperidone group and 66.6 (SD
49.84) mL in the placebo group.
Differences in breast milk volume between
the domperidone and placebo groups on day 7 of
treatment and day 10 (3 days after stopping treatment)
are shown in Table 2. Unpaired T-test revealed that
the domperidone group had significantly greater mean
breast milk volume than the placebo group on both
days (P=0.0001, for day 7 and day 10).

Mothers of preterm babies with

12 mothers excluded:
inadequate breast milk volume (n=64)
• infant gestational age > 37 weeks (4)
• maternal age > 30 years (3)
• maternal obesity (BMI > 30 kg/m2) (3)
ECG screening • twin delivery (2)
(n=52)

Normal ECG and lactation

counseling (n=52)
2 mothers excluded: infants died

Failed to lactate & randomized (n=50)

Physiotherapy + suctioning Suctioning alone

(n=24) (n=16)
1 mother dropped 3 mothers drop out:
out: infant died infants died
Breast milk volume measurement
physiotherapy

24 hrs before therapy Day 7 after therapy started Day 10 (3 days after
started therapy stopped)

Figure 1. Study profile

Paediatr Indones, Vol. 57, No. 1, January 2017 • 19

 Tengku Ellya Fazilla et al: Domperidone and maternal milk volume in mothers of premature newborns

Table 1. Baseline characteristics of subjects Table 3. Comparison of breast milk volume on days 7
Characteristics Domperidone Placebo group and 10 in the domperidone group
group (n=25) (n=25) Day of n Mean breast milk 95% CI of P value
Mean maternal age (SD), 26.8 (3.47) 25.7 (3.67) treatment volume (SD), mL differences
years Day 7 25 181.6 (80.26) -8.67 to 13.64 0.65
Mean number of children 1.9 (0.83) 1.7 (0.9) Day 10 25 179.1 (82.4)
born by mother (SD)
Method of delivery, n
Vaginal 14 11 None of our subjects complained of possible
Cesarean section 11 14 domperidone side effects, such as dry mouth,
Maternal education, n headache, abdominal pain, or tension in the breasts.
Primary school 8 7
Junior high school 4 5
Senior high school 12 13
Diploma 1 0 Discussion
Scholar/master 0 0
Employment, n
Government 0 0 In our study, the mean age of mothers who received
Private sector 0 0 domperidone was 26 years, with infants of 31 weeks
Enterpreneur 1 1
mean gestational age. Characteristics of subjects in
Farmer/fisherman 0 0
Housewife 24 24 this study were similar to those in a 2006 Canadian
Mean birth weight (SD), 1,656.8 (346.2) 1,636.8 (386.75) study. A previous study assessed domperidone effects
grams on breast milk production in subjects aged 28 years
Mean infant age (SD), 5.6 (6.75) 4.8 (4.42) who gave birth vaginally to infants of 29 weeks
days
Mean breast milk volume 83.3 (42.99) 66.6 (49.84)
gestation. They had only 16 subjects, whereas our
prior to therapy onset study involved 50 subjects, and they did not assess
(SD), mL the method of delivery, although Caesarean section
is known to be a risk factor for lactogenesis delay.6
However, our study showed no difference in breast
Table 3 shows the comparison of mean breast milk volume regarding method of delivery.
milk volume on day 7 of treatment and day 10 in We found significantly increased breast milk
the domperidone group. Paired T-test revealed no production in the domperidone group on day 7
significant differences in mean breast milk volume of treatment. Mean breast milk volume in the
(P>0.05) between day 7 and day 10. In the placebo domperidone group was 181.6 (SD 80.2) mL vs. 72.4
group, there were no significant differences in mean (SD 57.8) mL in the placebo group (95%CI 69.36
breast milk volume before treatment, day 7, and day to 148.93; P < 0.0001). This finding was consistent
10 (P >0.05). with a 2012 systematic review that assessed effects of
Multivariate linear regression analysis of number domperidone on lactation insufficiency in women who
of children, maternal education, and type of therapy gave birth to preterm and full-term infants. The results
on day 7 of treatment showed that type of therapy of three randomized, double-blind studies all showed
could be used to predict breast milk volume on day 7 of significant increases in breast milk production after
treatment (correlation strength 0.623). The equation administration of domperidone. Data analysis showed
was breast milk volume = 72.46 + 109.14 (therapy significant increases of 75.36% (95%CI 55.42 to 95.3;
type). Domperidone had a value of 1, while placebo P=0.00001) in daily breast milk production after taking
was given a value of 0. ANOVA test revealed P<0.05, domperidone compared to placebo. A limitation of this
so we concluded that the equation was appropriate. meta-analysis was that the three clinical trials had small

Table 2. Comparison of breast milk volume between the domperidone and placebo groups
Mean breast milk volume (SD), mL Domperidone group Placebo group 95% CI of differences P value
Day of treatment
Day 7 181.6 (80.26) 72.46 (57.84) 69.36 to 148.93 0.0001
Day 10 179.12 (82.4) 69.32 (51.74) 70.67 to 148.93 0.0001

20 • Paediatr Indones, Vol. 57, No. 1, January 2017

 Tengku Ellya Fazilla et al: Domperidone and maternal milk volume in mothers of premature newborns
sample sizes (17, 16, and 45 subjects each). Clinical
trials with small sample sizes may be subject to random
error.7 A large, multi-center study was conducted in
Toronto in 2012 as a randomized, double-blind clinical
trial of 560 mothers who gave birth to preterm babies.
This study was still running as of the writing of this
paper, as a protocol study.8
Domperidone increases breast milk production
by working as dopamine receptor antagonist in the
striata area, acting to inhibit the anterior pituitary
dopamine receptor or the tuberoinfundibular
system. Domperidone blocks the inhibitory effects of
dopamine-mediated prolactin secretion in the anterior
pituitary, resulting in increased serum prolactin
levels and thus, breast milk production.9,10,11 The
recommended dose of domperidone as a galactogogue
is 10 mg orally, administered 3 times per day for 1 to
2 weeks.7,12 However, there is no definitive guideline
on the domperidone dose that will increase breast
milk production. A randomized clinical trial with
double-blind design was conducted in Australia
on 6 mothers of preterm infants. Mothers received
domperidone at doses of 30 and 60 mg/day. Two-thirds
of subjects showed significant increases in breast
milk production and serum prolactin. The increase in
breast milk production occurred when the dose was
increased from 30 to 60 mg, although the amount of
domperidone in breast milk was quite low and has
minimal risk to breastfed babies.10 Another Canadian
study in 2012, compared two doses of domperidone
to increase breast milk production and found that an
increase of domperidone dose from 10 mg orally 3
times daily to 20 mg increased breast milk production,
similar to previous studies.8 However, Health Canada
issued a warning about domperidone doses exceeding
30 mg/day.13 We used a minimum dose of 10 mg orally
3 times per day as no Indonesian studies have assessed
the optimum dose of domperidone to increase breast
milk production. Moreover, this dose was chosen to
avoid possible side effects, especially arrhythmia.
The optimal duration of domperidone treatment
to increase breast milk production is unknown.
Previous studies used domperidone for 7, 10, and
14 days as well as 4 weeks. 2,8,14,15 All of these
studies showed increased breast milk production
after administering domperidone. We administered
domperidone for 7 days due to difficulty subject
compliance for taking medication and pumping breast
milk every 2 hours each day. Before the study began,
subjects underwent lactation counseling for 7 days and
were asked to pump their breast milk every 2 hours.
Hence, we required only 7 days of treatment in order
to improve subject adherence to the regimen.
Breast milk volume at day 7 of treatment was
not significantly different to that at 3 days after
stopping the treatment [181.6 (SD 80.26) mL vs.
179.1 (SD 82.4) mL, respectively (P=0.65)]. This
finding suggests that breast milk production remained
increased 3 days after stopping treatment.
Factors that were assessed for their effect on
breast milk volume in this study were number of
children borne by mother, maternal education, and
type of medication. Multivariate analysis showed that
type of medication with a strength of correlation of
0.623 could be used to predict breast milk volume on
day 7 of treatment.
Subjects had no complaints about side effects
such as dry mouth, headache, abdominal pain, or ten-
sion in the breasts. Arrhythmia is a serious side effect
that can occur. We assessed subjects for arrhythmias
by ECG examination and found no abnormalities in
all 50 subjects. With regards to possible side effects,
the Food and Drug Administration (FDA) in 2004
suggested that breastfeeding mothers not take dom-
peridone due to the risk of cardiac arrhythmias and
sudden death. These fates were observed in cancer
patients with low potassium levels who received high-
dose intravenous domperidone with chemotherapy.16
However, the FDA-issued warning was somewhat of
an overreaction, because the subjects who received
domperidone had comorbidities, were undergoing
chemotherapy, and had severe hypokalemia. In addi-
tion, the bioavailability of oral domperidone is only 13
to 17% and peak levels of domperidone at doses of 10
mg orally are only about 1/30 that of administration
via the parenteral route.13
Limitations of the study were that we did not
measure serum prolactin or domperidone levels in
breast milk, due to lack of measurement tools and
facilities in Haji Adam Malik Hospital. We also did not
assess the optimum dose and duration of domperidone
administration to maintain breast milk production.
Breast milk composition such as protein, glucose, and
lipid levels were also not determined in the study.
In conclusion, domperidone significantly in-
creases breast milk production compared to placebo
Paediatr Indones, Vol. 57, No. 1, January 2017 • 21
 Tengku Ellya Fazilla et al: Domperidone and maternal milk volume in mothers of premature newborns
in mothers who gave birth to preterm babies. In the
domperidone group, mean breast milk volume 3 days
after stopping treatment is not significantly different
from mean breast milk volume at day 7 of treatment.
No side effects associated with domperidone treat-
ment is found in our subjects.
Conflict of interest
None declared.
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